\r\n\tAn update on clinical manifestations, their assessment, monitoring, and imagiology, including peripheral arthritis, enthesopathy, and extra-articular findings, and, the differential diagnosis with other diseases which evolves with axial and peripheral calcifications will be provided.
\r\n
\r\n\t \r\n\tAn important component of this book must be dedicated to the more recent treatments namely with biologic therapies but focusing also on new small molecule inhibitors and experimental therapies.
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Member of the Comprehensive Health Research Center (CHRC), Nova medical School, University of Lisbon, and Director of the Oncology Service and Director of the Epidemiology and Molecular Biology Service (SEEBMO) at the Hospital de Santo Espirito de Angra do Heroísmo, Terceira Island, Azores, Portugal. Main research interests are the epidemiology and molecular genetics of Spondyloarthritis (SpA), Diffuse Idiopathic Skeletal Hyperostosis (DISH), and Chondrocalcinosis (CC). 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\n
1. Introduction to fungal disease
\n
Fungal infections are one of the most deadly infections accounting in excess of 1.5 million deaths annually worldwide. The major reason that makes fungal infections more life threatening because they are been neglected by the society. Though in last 20 years there are many developments in the diagnosis and treatment of fungal disease but still majority of population are devoid of the benefits of these developments [1]. Among all the fungal diseases, infection of skin hold the 4th position and it accounts for the majority of death also [2].
\n
Plant kingdom has always been a hub for many natural compounds with novel structure and this keep the investigators interested in doing research about many plants species till today. Results of new researchers showed that plants are enrich of many bioactive secondary metabolites such as saponins, alkaloids and terpenoids which characterized by antifungal property. Depending on that, these plants can be considered as a potent future source for anti-fungal drugs [3]. When recent scenario regarding fungal diseases and antifungal drugs are taken into consideration it has been seen that the development of resistance of fungus towards the presently used antifungal drugs has increased [4, 5, 6, 7, 8, 9, 10, 11]. With the challenges like morbidity and mortality there always lies difficulty in antifungal treatment for patients receiving therapy for AIDS, diabetes, chemotherapy or organ transplant as some of the molecular processes of fungus are similar to humans, so toxicity to fungal cells could affect human cells too [12]. In the last 30 years few drugs have made an impact in the treatment of fungal infection as shown in (Table 1), one of them is amphotericin B which is among the few fungicidal drugs present antifungal therapy has but it also showed several critical side effects (Table 2) [13]. In addition to this, during the period between late of 1980s and the beginning of 1990s emergence of Imidazoles and Triazoles was seen. These classes of drugs were efficient in inhibiting processes associated with fungal cells. The major drawback associated with them was relapse of infection and resistance developed by the fungus towards them [14]. Therefore, it become an oblige for the research to discover and produce a new, efficient, and safe anti-fungal treatments from new sources like plants. Therefore current chapter attempts to elaborate the current scenario about the important plants and their antifungal derivatives that can be future prospective to work on for development of more potent antifungal drugs.
There are around 2 million of fungal species found in the whole world but only 600 of them cause infection. The major species that are mostly involved in causing infection are Cryptococcus, Candida, Trichophyton and Aspergillus. All the fungal infections which affects human, that are prevailing in the world can be grouped into five types. The types are as follows:
Chronic lung or deep tissue infection: under this type example is chronic pulmonary aspergillosis
Allergic fungal disease: examples are allergic bronchopulmonary aspergillosis also known as ABPA and severe asthma with fungal sensitization (SAFS)
Mucosal infection: oral and esophageal candidiasis, Candida vaginitis are examples of this group.
Skin, hair and nail infection: examples of this kind of infections are athlete’s foot tinea capitis and onychomycosis [16].
\n\n
\n
\n
2. Plants having antifungal activity
\n
The epidemiological data suggest that the incidence and prevalence of serious mycoses continues to be a public health problem. The increased use of antifungal agents has resulted in the development of resistance to these drugs. The spread of multidrug-resistant strains of fungus and the reduced number of drugs available make it necessary to discover new classes of antifungals from natural products including medicinal plants. Medicinal plants have also been reported in traditional systems of medicine for the treatment of both human and animal mycoses, and are considered to be a valuable source for the discovery of new antifungal drugs. Many books have also reported and recorded the use of medicinal plants in the traditional system of medicine. Therefore, we have focused here mainly on the antifungal plants and their use against pathogenic fungi. The antifungal activity associated plants are illustrated in (Table 3).
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
S. No.
\n
Botanical name
\n
Family
\n
Parts used
\n
Chemical classes
\n
Microorganism tested
\n
\n\n\n
\n
1.
\n
Eugenia uniflora
\n
Myrtaceae
\n
Leaves
\n
Sesquiterpenes, Monoterpene, hydrocarbons
\n
C. albicans, C. dubliniensis, C. glabrata, C. krusei [17]
\n
\n
\n
2.
\n
Psidium guajava
\n
Myrtaceae
\n
Leaves
\n
Methanolic extract
\n
C. albicans, C. dubliniensis, C. glabrata, C. krusei [17]
\n
\n
\n
3.
\n
Curcuma longa
\n
Zingiberaceae
\n
Rhizome
\n
Turmeric oil
\n
C. albicans, C. dubliniensis, C. glabrata, C. krusei [17]
List of plants having antifungal activity against pathogenic fungi.
\n
\n
\n
3. Phytochemicals and their antifungal activity
\n
Plants and their biologically active chemical constituents, sometimes called secondary metabolites or bioactives, present numerous opportunities for the improvement of livestock production by inclusion in the diet. Several papers and reviews have been published on the occurrence of antifungal compounds in plant. However, literature and systematic reviews on the natural products as an alternative to antifungal drugs are still scanty. The distribution of antifungal compounds can be defined either on the basis of their taxonomic distribution or on the basis of their chemical classes. Table 4 shows the antifungal natural products belonging to all major classes of secondary metabolites such as phenolics, alkaloids, terpenoids, saponins, flavonoids, proteins, and peptides, etc.
\n
\n
\n
\n
\n
\n\n
\n
S. No
\n
Plants
\n
Plant part
\n
Phytochemicals
\n
\n\n\n
\n
1
\n
Aegle marmelos
\n
Leaves
\n
Essential oils
\n
\n
\n
2
\n
Alpinia galangal
\n
Seeds
\n
Diterpenes
\n
\n
\n
3
\n
Ananas comosus
\n
Leaves
\n
Protein
\n
\n
\n
4
\n
Blumea balsamifera
\n
Leaves
\n
Flavonoid luteolin
\n
\n
\n
5
\n
Camptotheca acuminate
\n
Leaves
\n
Flavonoid
\n
\n
\n
6
\n
Capsicum frutescens
\n
Whole plant
\n
Triterpene saponin
\n
\n
\n
7
\n
Cassia tora
\n
Whole plant
\n
Emodin, physcion and rhein
\n
\n
\n
8
\n
Datura metel
\n
Whole plant
\n
Alkaloid
\n
\n
\n
9
\n
Euonymus europaeus
\n
Leaves
\n
Protein
\n
\n
\n
10
\n
Haloxylon salicornium
\n
Aerial part
\n
Alkaloid
\n
\n
\n
11
\n
Juniperus communis
\n
Leaves
\n
Essential oil
\n
\n
\n
12
\n
Khaya ivorensis
\n
Stem bark
\n
Triterpenes
\n
\n
\n
13
\n
Lycium chinense
\n
Root bark
\n
Phenolic compounds
\n
\n
\n
14
\n
Musa acuminate
\n
Banana
\n
Protein
\n
\n
\n
15
\n
Ocimum gratissimum
\n
Bark
\n
Essential oil
\n
\n
\n
16
\n
Pinus pinaster
\n
Leaves
\n
Pinosylvin
\n
\n
\n
17
\n
Polygonum punctatum
\n
Whole plant
\n
Sesquiterpene
\n
\n
\n
18
\n
Smilax medica
\n
Root
\n
Saponins
\n
\n
\n
19
\n
Solanum tuberosum
\n
Tubers
\n
Protein
\n
\n
\n
20
\n
Thymus vulgaris
\n
Whole plant
\n
Essential oil
\n
\n
\n
21
\n
Trachyspermum ammi
\n
Leaves, flowers
\n
Essential oil
\n
\n
\n
22
\n
Trigonella graecum
\n
Whole plants
\n
Peptides
\n
\n
\n
23
\n
Zingiber officinalis
\n
Rhizome
\n
Protein
\n
\n\n
Table 4.
List of plant components having antifungal property [29].
\n
\n
\n
4. Novel approaches for antifungal plant components and their extracts
\n
Novel drug delivery system has shown tremendous potential to deliver herbal drugs in the form of microcapsules, implants, nanoparticles micro particles sustained release tablets or extended release forms. Many herbal drugs using novel drug delivery system has made a mark in the market and few of them are in the developmental stage in the laboratory [30].
\n
Active herbal components such as curcumin, digoxin, atropine, bromelain can be promising prospects for treatment of conditions like cancer or inflammation [31].
\n
The popularity experienced by novel drug delivery system is due to its ability to deliver the herbal drugs in a better way providing enhanced therapeutic efficacy with lower toxicity [32]. In addition to this it also counteract the limitations of lower absorption and lack of specificity experienced by the available formulation of drugs. Advantages of novel drug delivery system over the presently available drug therapy is that it is specific, has rapid onset of action with faster absorption due to enhanced surface area and lastly nanoparticles provides better penetration in Blood Brain Barrier (BBB) [33].
\n
For any herbal drugs to show expected therapeutic efficacy optimum amount of active constituent must reach the target tissues. Herbal drugs are prone to be degraded by first pass metabolism of by the pH difference of GIT. Various novel drug delivery systems such as nanoparticles, nanoemulsions, phytosomes, transferosomes and liposomes by passes all the hurdles of acidic pH as well as first pass metabolism to carry optimum amount of drugs to target tissues. Being smaller in size nano carriers also provides rapid onset of actions [34].
\n
For delivery of drug by using novel drug delivery system, herbal drugs present themselves as potential candidate because of following reasons:
The side effects that are seen with other drugs are absent with natural compounds.
Natural compounds shows synergistic effect when they contain multifunctional molecules.
Natural compounds have traditional backing for their action and safety potential whereas modern medicines are more toxic even if they are experimentally proven for their action [35].
\n\n
\n
4.1 Novel carrier systems used to treat different fungal infections
\n
The major benefit provided by novel drug delivery system is to elicit better therapeutic response with minimum doses. Types of carriers used for herbal drug delivery and synthetic drugs are as follows:
\n
\n
4.1.1 Phytosomes
\n
The name came from two words “Phyto” and “some” which means plant and cell-like respectively. Phytosomes contains lipid soluble complex of phospholipids and phyto-constituents. Some literatures also referred Phytosomes as ribosome [36]. Green tea phytosomes, Ginkgo biloba phytosomes, Centella phytosomes, Meriva phytosome, Zanthalene phytosomes, Sericoside phytosomes are some examples of phytosomes which are recently developed and characterized for different ailments. Among all of them Zanthalene phytosomes are prepared especially for the treatment of fungal disease.
\n
Advantages of Phytosomes
Phytosomes are not degraded by bacteria or digestive secretion of guts.
It has better stability because of the formation of bonds chemically connecting phytoconstituents and phosphatidylcholine molecules.
Phytosomes delivers herbal drug to the respective target tissues [37].
It shows greater therapeutic benefit due to better absorption of lipid insoluble polar phytoconstituents in turn shows better bioavailability [38].
\n\n
\n
\n
4.1.2 Liposomes
\n
Liposomes contain microscopic vesicles made up of lipid bilayer arranged in concentric fashion and the separation is filled with aqueous medium. Lipophilic substances are inserted into the lipid bilayer whereas aqueous compartment traps hydrophilic substance. Liposomes show better bioavailability, stability and enhanced pharmacokinetic property [39]. There are various herbal and synthetic liposomes are prepared for the effective treatment of different skin diseases. In 2017, a herbal liposomal gel containing ketoconazole and neem extract was developed for the effective treatment of seborrheic dermatitis against Aspergillus niger and Candida albicans. The results indicated that developed liposomal gel have great potential and showed synergetic effect for the treatment.
\n
Advantages of liposomes
Liposome formulation is better options for producing sustained release formulations as it enhances drug solubility.
It is easy to load phytoconstituents of any chemical nature whether it is hydrophilic, amphiphilic or lipophilic [40].
\n\n
\n
\n
4.1.3 Nanoparticles
\n
This carrier system has particle size within the range between 1 and 100 nm. The particles which are of nano size are made up of polymer of synthetic or semisynthetic origin. Nanoparticles are microencapsulated to protect them from any kind of losses. Nanoparticles were made to encounter the problem of solubility and toxicity associated with triptolide [41].
\n
Advantages of herbal nanoparticle delivery system:
Nanoparticles having smaller size shows better dissolution in turn enhances solubility of dosage form and it also delivers drug with specificity thereby enhancing the efficacy [42].
\n\n
\n
\n
4.1.4 Microemulsions and nanoemulsion
\n
These are emulsions of O/W type and the particle size of the particulate is of micron. In this drug delivery system inner phase stores the drugs and because of its contact with tissue directly drug release is slow. As per few reports oil of Pterodon emarginatus are considered to have property to enhance anti-inflammatory activity [43]. Formulation, development and evaluation of microemulsion gel of hydroalcoholic extract of Quercus infectoria in the treatment of different skin ailments was successfully prepared. Tannins which are prime constituent of galls can be effectively treat different skin conditions.
\n
\n
\n
4.1.5 Microsphere
\n
This drug delivery system have matrix and the drug is dispersed in a polymer which are present inside this matrix. Particle size that can be used is in between 1 and 300 μm. The release of drug is dependent on the dissolution and degradation rate of the said matrix. Release of drug occurs according to first order kinetic. For example, development and evaluation of floating microspheres of curcumin prepared by emulsion solvent diffusion method for treatment of onychomycosis. The result shows improved absorption kinetics of curcumin.
\n
Advantages of microsphere formulations
The major advantage of this kind of formulation is that it taken orally or parentally and their site of release can also be targeted [44].
\n\n
\n
\n
4.1.6 Niosomes
\n
Niosomes are similar as liposomes bjt are far more stable than liposomes. Niosomes are made up of surfactant like dialkyl polyglycerol which is noninonic in nature and are able encapsulate variety of drugs. Niosomes are more economical than liposomes [32]. Chitosan niosomal gel, miconazole niosomes are prepared as an effective nanocarrier against both dermatophytes and yeasts.
\n
\n
\n
\n
4.2 Transdermal drug delivery system
\n
In this system of drug delivery, patches encapsulating drugs are prepared and are placed on the skin. Through the skin drug enters into the blood vessels. This system is beneficial when the required effect of oral therapy was not found to be up to the mark. Patches of antismoking and anti-motion sickness are available in market [45].
\n
Advantages of transdermal drug delivery
The transdermal delivery system has advantages such as it provides enhanced bioavailability and provides a better alternative of dosage form for unconscious or vomiting patients [46].
\n\n
\n
4.2.1 Ethosomes
\n
Ethosomes are composed of phospholipids and ethanol and are in the form of sac. Ethanol present in ethosomes acts as permeability enhancer. Ethosomes are found in the form of cream and gel for better patient compliance [47]. Now a days, Transethosomes and Nanoethosomes used most widely which are the advanced type of ethosomes having edge activator in it. These advanced novel carrier system is much better than conventional novel carriers like transferosomes and liposomes [48]. Clotrimazole, Itraconazole, Miconazole are synthetic drugs which are prepared and evaluated successfully for the treatment of dermatophytosis or ringworm. Tridax procumbens and Galinsoga parvifolia are two herbs used into ethosomal gel against Trichophyton species.
\n
Advantages of Ethosome
Ethosomes can entrap all type of drugs and have better skin permeability [46].
\n\n
\n
\n
4.2.2 Transferosomes
\n
Transferosomes contains phospholipids sac which behaves as carrier for delivery of drug through the skin. As Transferosomes are flexible in nature they cross the skin through the intracellular space found within the skin. Transferosomes of Colchicines shows lesser side effect than its oral form [49].
\n
Advantages of Transferosomes:
Transferosomes being flexible can pass through narrow openings of skin.
It shows high efficiency of entrapment which may increase up to 90% in case of lipophilic drug [50].
\n\n
\n
4.2.2.1 Complexation
\n
The problem associated with herbal drug formulation is their solubility. To counter this solubility problem, complex formation is done which gives particulates with well-defined stoichiometry. Few commonly used complexing agents are EDTA and cyclodextrin [51].
\n
\n
\n
4.2.2.2 Hydrogels
\n
The hydrogel are three dimensional structures with cross linking of polymers. As name suggest hydrogels are hydrophilic in nature. Hydrogels can be designed into different forms according to the needs. The form can be of slabs, films and nanoparticle coating [52]. Hydrogels have the potential to bind both herbal as well as synthetic drug, this ability can be treated as avenue for further research [53]. There are many marketed formulation of novel drug delivery available in the market [46, 54] Here are list of some novel carriers used with their plant components or synthetic drugs combinations for different fungal infections (Table 5).
\n
\n
\n
\n
\n
\n\n
\n
Drugs/Plant components
\n
Novel carriers
\n
Indication
\n
Microorganism tested
\n
\n\n\n
\n
Essential oil (Bidens tripartite)
\n
Microemulsion gel
\n
Candidiasis
\n
Candida albicans
\n
\n
\n
Curcumin
\n
Phytosome
\n
Onychomycosis
\n
Yeast sp.
\n
\n
\n
Clotrimazole, Econazole nitrate, Fluconazole
\n
Micelles
\n
Superficial fungal infection
\n
Trichophyton sp.
\n
\n
\n
Miconazole
\n
Solid lipid nanoparticles and nanostructured lipid carriers
List of some novel carriers for antifungal plant components and synthetic drugs [55].
\n
\n
\n
\n
\n
\n
5. Conclusion
\n
The last 20 years has shown an increase in number of fungal infection. Currently used drugs in treatment of fungal infection are having many side effects, and development of resistance is very common against these drugs. Plants have been considered as traditional source of antifungal medicines for past many years. Plant bioactive with antifungal activity can be considered as an option for development of new and improved alternative formulations in antifungal therapy. Development of improved formulations with plant phytcompounds is the need of the hour for efficient treatment of fungal diseases. Further research on this field can provide us with increased number of options in treatment of fungal diseases that will give the patients with a better quality of life.
\n
\n\n',keywords:"antifungal, phytocompounds, fungicidal, antifungal therapy, fungal infections",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/70638.pdf",chapterXML:"https://mts.intechopen.com/source/xml/70638.xml",downloadPdfUrl:"/chapter/pdf-download/70638",previewPdfUrl:"/chapter/pdf-preview/70638",totalDownloads:1791,totalViews:0,totalCrossrefCites:1,totalDimensionsCites:6,totalAltmetricsMentions:4,impactScore:4,impactScorePercentile:91,impactScoreQuartile:4,hasAltmetrics:1,dateSubmitted:"May 22nd 2019",dateReviewed:"November 27th 2019",datePrePublished:"March 4th 2020",datePublished:"March 25th 2020",dateFinished:"December 26th 2019",readingETA:"0",abstract:"In the past few decades, a worldwide increase in the incidence of fungal infections has been observed as well as rise in the resistance of some species of fungi to different fungicidal used in medicinal practice. Besides, fungi are the one of the most neglected pathogens as demonstrated by the fact that the amphotericin B and other sold treatments are still used as gold standard as antifungal therapy. The majority of used antifungal treatments have various drawbacks in terms of toxicity, efficacy as well as cost and their frequent use has also led to the emergence of resistant strains. Hence, there is a great demand for developing an antifungal belonging to a wide range of structural classes, selectively acting on new targets with least side effects. Natural products, either as pure phytocompounds or as standardized plant extracts, provide unlimited opportunities for new drug lads because of their having normally matchless chemical diversity. Present chapter focused on the work done in the field of antifungal activities of various plant components and novel approaches which will be the future prospective for the new drug discoveries and providing better antifungal therapy.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/70638",risUrl:"/chapter/ris/70638",book:{id:"9108",slug:"medicinal-plants-use-in-prevention-and-treatment-of-diseases"},signatures:"Koushlesh Kumar Mishra, Chanchal Deep Kaur, Anil Kumar Sahu, Rajnikant Panik, Pankaj Kashyap, Saraswati Prasad Mishra and Shweta Dutta",authors:[{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",fullName:"Anil Kumar Sahu",slug:"anil-kumar-sahu",email:"anil2484@gmail.com",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",institution:{name:"Chhattisgarh Swami Vivekanand Technical University",institutionURL:null,country:{name:"India"}}},{id:"211230",title:"Mr.",name:"Pankaj",middleName:null,surname:"Kashyap",fullName:"Pankaj Kashyap",slug:"pankaj-kashyap",email:"pankajkashyap333@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"221419",title:"Mr.",name:"Koushlesh",middleName:null,surname:"Mishra",fullName:"Koushlesh Mishra",slug:"koushlesh-mishra",email:"koushleshmishra@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"221420",title:"Mr.",name:"Sarawati Prasad",middleName:null,surname:"Mishra",fullName:"Sarawati Prasad Mishra",slug:"sarawati-prasad-mishra",email:"saraswatim3@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"270359",title:"Dr.",name:"Chanchal Deep",middleName:null,surname:"Kaur",fullName:"Chanchal Deep Kaur",slug:"chanchal-deep-kaur",email:"dr.chanchaldeep@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"314683",title:"Dr.",name:"Rajnikant",middleName:null,surname:"Panik",fullName:"Rajnikant Panik",slug:"rajnikant-panik",email:"panik.143@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"314684",title:"Ms.",name:"Shweta",middleName:null,surname:"Dutta",fullName:"Shweta Dutta",slug:"shweta-dutta",email:"shweta.run46@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction to fungal disease",level:"1"},{id:"sec_2",title:"2. Plants having antifungal activity",level:"1"},{id:"sec_3",title:"3. Phytochemicals and their antifungal activity",level:"1"},{id:"sec_4",title:"4. Novel approaches for antifungal plant components and their extracts",level:"1"},{id:"sec_4_2",title:"4.1 Novel carrier systems used to treat different fungal infections",level:"2"},{id:"sec_4_3",title:"4.1.1 Phytosomes",level:"3"},{id:"sec_5_3",title:"4.1.2 Liposomes",level:"3"},{id:"sec_6_3",title:"4.1.3 Nanoparticles",level:"3"},{id:"sec_7_3",title:"4.1.4 Microemulsions and nanoemulsion",level:"3"},{id:"sec_8_3",title:"4.1.5 Microsphere",level:"3"},{id:"sec_9_3",title:"4.1.6 Niosomes",level:"3"},{id:"sec_11_2",title:"4.2 Transdermal drug delivery system",level:"2"},{id:"sec_11_3",title:"4.2.1 Ethosomes",level:"3"},{id:"sec_12_3",title:"Table 5.",level:"3"},{id:"sec_12_4",title:"4.2.2.1 Complexation",level:"4"},{id:"sec_13_4",title:"Table 5.",level:"4"},{id:"sec_17",title:"5. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'\nSanglard D. Clinical relevance of mechanisms of antifungal drug resistance in yeasts Importancia clínica de los mecanismos de resistencia a los antifúngicos en levaduras. Enfermedades Infecciosasy Microbiología Clínica. 2002;20(9):462-470\n'},{id:"B2",body:'\nHay RJ, Johns NE, Williams HC, Bolliger IW, Dellavalle RP, Margolis DJ, et al. The global burden of skin disease in 2010: An analysis of the prevalence and impact of skin conditions. The Journal of Investigative Dermatology. 2013;134(6):1527-1534. DOI: 10.1038/jid.2013.446\n'},{id:"B3",body:'\nArif T, Bhosale JD, Kumar N, Mandal TK, Bendre RS, Lavekar GS, et al. Natural products–antifungal agents derived from plants. Journal of Asian Natural Products Research. 2009;11(7):621\n'},{id:"B4",body:'\nFischer MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC, McCrwa SL, et al. Emerging fungal threats to animal, plant and ecosystem health. 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Natural Product Research. 2006;20:842-849\n'},{id:"B21",body:'\nPortillo A, Vila R, Freixa B, Adzet T, Canigueral S. Antifungal activity of Paraguayan plants used in traditional medicine. Journal of Ethnopharmacology. 2001;76:93-98\n'},{id:"B22",body:'\nEndo K, Kanno E, Oshima Y. Structures of antifungal diarylheptenones, gingerenones a, B, C and isogingerenone B, isolated from the rhizomes of Zingiber officinale. Phytochemistry. 1990;29:797\n'},{id:"B23",body:'\nDabur R, Chhillar AK, Yadav V, Kamal PK, Gupta J, Sharma GL. In vitro antifungal activity of 2-(3,4-dimethyl-2,5-dihydro-1H-pyrrol-2-yl)-1-methylethyl pentanoate, a dihydro – Pyrrole derivative. Journal of Medical Microbiology. 2005;54:549-552\n'},{id:"B24",body:'\nIngham JL, Tahara S, Harborne JB. Fungitoxic isoflavones from Lupinus albus and other Lupinus species. Zeitschrift für Naturforschung. 1983;38c:194-200\n'},{id:"B25",body:'\nHar-Nun N, Meyer AM. Cucurbitacins protect cucumber tissue against infection by Botrytis cinerea. Phytochemistry. 1990;29:787-791\n'},{id:"B26",body:'\nKim KY, Davidson PM, Chung HJ. Antibacterial activity in extracts of Camellia japonica L. petals and its application to a model food system. Journal of Food Protection. 2001;64:1255-1260\n'},{id:"B27",body:'\nKobayashi K, Nishino C, Tomita H, Fukushima M. Antifungal activity of pisiferic acid derivatives against the rice blast fungus. Phytochemistry. 1987;26:3175-3179\n'},{id:"B28",body:'\nIto T, Kumazawa K. Antifungal substances from mechanically damaged cherry leaves (Prumus yedoensis matsumura). Bioscience, Biotechnology, and Biochemistry. 1992;56:1655\n'},{id:"B29",body:'\nMeena MR, Sethi V. Antimicrobial activity of essential oils from species. Journal of Food Science and Technology. 1994;31:68-70\n'},{id:"B30",body:'\nDevi VK, Jain N, Valli SK. Importance of novel drug delivery systems in herbal medicines. Pharmacognosy Reviews. 2010;4(7):27-31\n'},{id:"B31",body:'\nYadav D, Suri S, Chaudhary AA, Asif M. A novel approach: Herbal remedies and natural products in pharmaceutical science as nano drug delivery systems. International Journal of Pharmacy and Technology. 2011;3(3):3092-3116\n'},{id:"B32",body:'\nBeyatricks KA, Kumar KS, Suchitra D, Jainab HN, Anita A. Recent microsphere formulation and its applications in herbal drugs. International Journal of Pharmaceutical Development and Technology. 2014;4(1):58-62\n'},{id:"B33",body:'\nChakraborty K, Shivakumar A, Ramachandran S. Nanotechnology in herbal medicine. International Journal of Herbal Medicine. 2016;4(3):21-27\n'},{id:"B34",body:'\nIndalkar YR, Pimpodkar VP, Godase AS, Gaikwad PS. A compressive review on the study of nanotechnology for herbal drugs. Asian Pharma Press. 2015;5(4):203-207\n'},{id:"B35",body:'\nSharma AT, Mitkare SS, Moon RS. Multicomponent herbal therapy: A review. 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International Journal of Drug Delivery Technology. 2016;6, 26(1):7\n'},{id:"B41",body:'\nAbirami A, Halith SM, Pillai KK, Anbalagan C. Herbal nanoparticle for anticancer potential - a review. World Journal of Pharmacy and Pharmaceutical Sciences. 2014;3(8):2123-2132\n'},{id:"B42",body:'\nSachan AK, Gupta A. A review on nanotized herbal drugs. International Journal of Pharmaceutical Sciences and Research. 2015;6(3):961-970\n'},{id:"B43",body:'\nJadhav V, Bhogale V. Novel drug delivery system in herbal. International Journal of Pharma Wave. 2015;1(2):85-103\n'},{id:"B44",body:'\nPascoa H, Diniz DA, Florentino IF, Costa EA, Bara MF. Microemulsion based on Pterodon emarginatus oil and its anti inflammatory potential. Brazilian Journal of Pharmaceutical Sciences. 2015;51(1):117-126\n'},{id:"B45",body:'\nAmol K, Pratibha P. Novel drug delivery system in Herbal’s. International Journal of Pharmaceutical, Chemical and Biological Sciences. 2014;4(4):910-930\n'},{id:"B46",body:'\nYadav M, Bhatia VJ, Doshi G, Shastri K. Novel techniques in herbal drug delivery systems. International Journal of Pharmaceutical Sciences Review and Research. 2014;28(2):83-89\n'},{id:"B47",body:'\nGhulaxe C, Verma R. A review on transdermal drug delivery system. The Pharma Innovation Journal. 2015;4(1):37-43\n'},{id:"B48",body:'\nMishra KK, Kaur CD, Verma S, Sahu AK, Dash DK, Kashyap P, et al. Transethosomes and nanoethosomes: Recent approach on transdermal drug delivery system. Nanomedicine. 2019;2:33-54\n'},{id:"B49",body:'\nFatima GX, Rahul RS, Reshma I, Sandeep T, Shanmuganathan S, Chamundeeswari D. Herbal ethosomes - a novel approach in herbal drug technology. American Journal of Ethnomedicine. 2014;1(4):226-230\n'},{id:"B50",body:'\nAjazuddin S. Applications of novel drug delivery system for herbal formulations. Fitoterapia. 2010;81:680-689\n'},{id:"B51",body:'\nSachan R, Parashar T, Soniya SV, Singh G, Tyagi S, Patel C, et al. Drug carrier transferosomes: A novel tool for transdermal drug delivery system. International Journal of Research and Development in Pharmacy & Life Sciences. 2013;2(2):309-316\n'},{id:"B52",body:'\nButler MS. The role of natural product chemistry in drug discovery. Journal of Natural Products. 2004;67(12):2141-2153\n'},{id:"B53",body:'\nKushwaha SKS, Rastogi A, Rai AK, Singh S. Novel drug delivery system for anticancer drug: A review. International Journal of PharmTech Research. 2012;4(2):542-553\n'},{id:"B54",body:'\nLai WF, Al R. Hydrogel based materials for delivering herbal drugs. ACS Applied Materials & Interfaces. 2017;9(13):11309-11320\n'},{id:"B55",body:'\nBseiso EA, Nasr M, Sammour O, Gawad NA. Recent advances in topical formulation carriers of antifungal agents. Indian Journal of Dermatology, Venereology and Leprology. 2015;8(5):457-463\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Koushlesh Kumar Mishra",address:"koushleshmishra@gmail.com",affiliation:'
Shri Rawatpura Sarkar Institute of Pharmacy, India
'},{corresp:null,contributorFullName:"Chanchal Deep Kaur",address:null,affiliation:'
Shri Rawatpura Sarkar Institute of Pharmacy, India
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\n
1. History, development, and advantages of speed machining
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Machining with high cutting speeds is associated with the name Carl Salamon [1]. This German researcher in the 1920s milled, for example, steel with cutting speeds at 440 m.min−1, and aluminum at up to 16,500 m.min−1. The trials ended in German Patent No 523594 of 1931, creating a series of diagrams describing the impact of the cutting speed on the cutting temperature (Figure 1). The experiment focused on machining non-ferrous metals, such as aluminum, copper, and brass, respectively [1]. The theory assumes that at a certain cutting speed (5–10 times higher than in conventional machining), the chip removal temperature at the cutting edge will start to decrease.
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Figure 1.
Machining temperatures at high speeds.
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His experiments overturned Taylor’s theory on “maximum cutting speeds,” above which machine damage would occur. Salomon showed that for each tool-work piece couple, there exists a critical speed range at which machining is not possible. After overcoming this area, we can continue to work, while the temperature of cutting will drop significantly. In the early 1950s, research in the USA carried on from his results. For cutting thin-walled aircraft parts, the Lockhead and Boeing corporations, on a spindle mounted on rolling bearings (nmax = 18,000 min−1, Pelm = 18 kW), achieved a milling speed of 3000 m.min−1, [1, 2, 3]. In 1978 in Germany, and a year later in the USA, extensive research focused on the practical usage of high-speed machining was begun. In Germany alone, more than 40 leading firms participated on a project. On the basis of this cooperation at the beginning of 1980 at a university in Darmstadt was constructed an integrated milling spindle unit with asynchronous drive, with a spindle mounted on active magnetic bearings and cutting speeds of 2000–10,000 m.min−1 [4]. Over the next 3 years,, an economic variant on a roller bearing was constructed. Partial results from ongoing research confirmed the following advantages of high-speed milling:
at increased cutting and feed speeds, the cutting force is significantly reduced, [3, 4]. This makes possible the machining of thin-walled parts without special preparations. A drop in cutting forces reduces the demands for rigidity of the whole machine;
a large part of the heat emerging in the machining process is taken away by chips. This significantly increases the durability of the machine, the work piece remains cold, and the roughness of its surface is decreased with equal or better dimensional precision, which leads to a saving in finishing operations;
a significant increase in cutting power leads to saving production time so as to save of production costs; and
high-speed cutting machine provides higher quality surface finish due to the reduced cutting pressure.
\n\n
A comparison of the advantages and disadvantages of conventional and high-speed machining is shown in the following table (Table 1).
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\n
\n
\n\n
\n
Technology of classical machining
\n
High-speed machining technology
\n
\n\n\n
\n
The contact time between tool and work is large
\n
Contact time is short
\n
\n
\n
Less accurate work piece
\n
More accurate work piece
\n
\n
\n
Cutting force is large
\n
Cutting force is low
\n
\n
\n
Poor surface finish
\n
Good surface finish
\n
\n
\n
Material removal rate is low
\n
Material removal rate is high
\n
\n
\n
Cutting fluid is required
\n
Cutting fluid is not required
\n
\n\n
Table 1.
Compare technology of classical machining a HSC technology.
\n
\n
\n
2. Parameters of high-speed machining
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Cutting speed values in chip machining are dependent on technology, the material make-up of the cutting machine, and of the machined pieces. Therefore, there exists no unequivocal and general classification of machining according to cutting speeds. In professional literature, we most often encounter the concepts of classical, high-speed, and ultra-high-speed machining. It should be noted, however, that the classifications of the individual authors are considerably different or contradictory. According to individual machining technologies, König is probably the most systematic classification of cutting speeds [3, 4]. This author divides machining into classic and high speed (Figure 2). Back in the 1950s, Kronenberg carried out experiments with ultra-high cutting speeds of 9000–720,000 m.min−1. In Figure 2, it can be seen that for stretching technology, the area of high-speed machining is in the 30–70 m.min−1 range, whereas in this area, cutting speeds from about 5000 to 12,000 m.min−1 are used for grinding.
The dependence of cutting speed for individual types of machined material is shown in Figure 3 [4]. It is clear from the figure that the lowest cutting speed is when milling nickel and its alloys and the highest when milling aluminum and its alloys.
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Figure 3.
Cutting speed ranges for milling.
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It must be remembered that cutting speed is also a function of the cut material and other accompanying machining conditions (cooling, etc.). To create the most general idea of cutting speed values, we can break down machining according to Figure 4.
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Figure 4.
Outlining of cutting speed ranges for speed machining: (A) classic machining, (B) transitional area, (C) high-speed machining, and (D) ultra-high-speed machining.
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\n
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3. Headstock—heart of machine tool
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The issue of high-speed machining is very expansive. It is suitable therefore to divide this area into the conception of the machine as a unit and the development of its individual constructional nodes and elements.
\n
Modern machine tools have become more flexible capable of performing a range of programmed tasks.
\n
In the conception of a machine, it is necessary to bring into consideration these factors:
in the design of a machine’s frame, it is important to place emphasis on rigidity and damping capacities. It is very advantageous for this purpose to select the machine frame in high-strength concrete;
the working area of the machine must be perfectly shroud covered, with good chip transfer and with a suitably selected cooling and control system;
feed units must be designed with consideration of maximum speeds (vr—15-20 m. min−1), with very short time constants and high strengthening factors (kv ›1.8). This means on one side reducing to a minimum the weight of the moving parts, and on the other, securing maximum rigidity. We can solve this compromise by using high-strength lightweight materials; and
also important are the aspects of the modularity of the machine construction, together with the rapid replacement of the spindle unit and other machine nodes.
\n\n
The headstock, as a construction node, has an important position in the overall machine concept. This is for the following reasons:
the spindle should rotate with the high degree of accuracy. The accuracy of rotation is determined by the axial and radial run out of the spindle nose and these must not exceed certain permissible values that are specified depending upon the required machining accuracy. The rotational accuracy is influenced at the most by the stillness and accuracy of the spindle bearings, particularly the one located at the front end;
the spindle unit must have high static stiffness. The stiffness of the unit is made up of the stiffness of the spindle unit proper and the spindle bearings. Machining accuracy is influenced on bending, axial as well as torsional stiffness. In series configurations of individual machine nodes, headstock is usually the weakest construction node, which is a limiting member to achieve the required rigidity of the entire machine concept, as a criterion for ensuring the required standstill accuracy;
the spindle unit must have high dynamic stiffness and damping. Poor dynamic stability of the spindle unit adversely affects the dynamic behavior of the machine tool as a whole; and
the maximum rotational frequencies of the headstock is a limiting factor of the maximum cutting speed of machine tools and thus of the overall machine production. These maximum rotational frequencies can no longer be ensured for HSC by conventional indirect drives with gear or belt. It should be emphasized that these two factors, stiffness and maximum speed, act in opposite directions.
\n\n
For high-speed machining, headstocks with integrated drive—“Electrospindles”—are usually used (Figure 5) [5]. This has solved the problem of providing rotational frequencies for high cutting speed.
\n
Figure 5.
Spindle unit with integrated drive (SKF) [5].
\n
The electrospindle consists of the particular parts and external peripheries, which together provide the required functions of the whole assembly group (Figure 6) [6]. The essential headstock parts include the spindle, bearings system, the tool clamping system or the work piece chucking system, and the body of the headstock. The peripheral devices can include integrated or external systems determined to drive the spindle, lubricate the bearings, provide cooling, spindle indexing, and monitoring.
\n
Figure 6.
Headstock morphology.
\n
\n
\n
4. Box of headstock
\n
For high-speed machining, tubular shapes of headstocks like box type are more used. Recently, in addition to tubes made of steel, bodies with a tube wound from fiber composites have recently been used. These include headstocks from Weiss or Step-tech. Based on the elasticity and rigidity knowledge, it is possible to form the approximate solution of every headstock type. Requirements put on the headstock body boxes are:
maximum symmetry—for the reasons of symmetrical thermal expansions;
minimum quantity of holes—holes decrease rigidity; and
The requirements put on the spindle are concentrated on the spindle geometric rigidity, selection of design material, and shape configuration of diameters. The selection of design material for the spindle is conditioned particularly by mechanical properties of the essential core structure, which are by the modulus of elasticity E and by the coefficient of relative damping D. The spindles made of steel comply with the requirements of high static rigidity. The relative spindle quality measure is its specific rigidity, that is, the spindle nose rigidity compared with the spindle weight. The spindle natural frequency and the dynamic characteristics of the headstock are also connected with it. Composite materials (graphite epoxide) start to be used for high-speed spindles. This spindle is lighter, and it does not require such a big diameter [7].
\n
The shape configuration of diameters shall be simple to the maximum possible extent. Those configurations are rational, where the minimum number of graduated diameters can be found and the difference between diameters is determined only by the types and dimensions of applied bearing models.
\n
The spindle end that protrudes from the headstock body is called the front spindle nose. When designing the spindle, the great attention must be paid to the suitable adaptation of the spindle nose so that it can provide the optimum tool clamping (through the clamping shank) or the optimum work piece chucking (e.g., by means of the chuck) [8]. This connection must be a quick, precise, rigid, and reliable one. The type execution and the shape of the spindle nose depend on the technology, type, and size machine tool and on the required accuracy of working.
\n
\n
\n
6. Spindle bearing system
\n
A limiting factor determining cutting speed is bearings. At high frequencies, it must be sufficiently rigid, accurate, and with high durability. The selection of the bearing type in particular supports in the bearing system of the machine tool spindle is always the matter of a compromise among the high rigidity, maximal frequencies of rotation, and offered possibilities of the utilizable building area in the headstock body. In particular, electromagnetic and rolling bearing nodes made of radial angular contact ball bearings are used for receiving spindles for high-speed machining. High revolutions may be achieved by the application of an aero-static bearing whose very low rigidity makes it suitable only for grinding operations.
\n
\n
6.1 Electromagnetic bearings
\n
In the mid-twentieth century, a successful magnetic levitation bearing was successfully demonstrated. This first successful magnetic bearing utilized electromagnets to provide attractive forces in the five degrees of freedom (with rotation being the sixth). Active servo control stabilized the system by using feedback signals from position sensors in each axis of control to vary the currents flowing through the various electromagnets.
\n
Several individual electromagnets, usually from 8 to 12, were arranged in a north-south-north-south configuration around each end of a levitated shaft to provide radial support. This design approach, which results in a multiplicity of magnetic flux reversals around the circumference of the shaft, is known as heteropolar. Most commercially available magnetic bearing systems utilize this technology. A typical heteropolar magnetic bearing system is shown in the below Figure 7 [9].
\n
Figure 7.
Principle of electromagnetic bearings.
\n
The stator, composed of an array of stationary electromagnets, generates powerful attraction forces that suspend the ferrous rotor shaft in the center of the magnetic field (with the help of an active servo-control unit). The active magnetic bearings are divided into radial, axial, and conical bearings (Figure 8).
\n
Figure 8.
Type of magnetic bearings.
\n
In addition to the zero mechanical passive resistances, these active bearings have the property that they can determine, for example, the cutting force value, thanks to the active check of the bearing. The reached maximum speed is up to 100,000 min−1 and at small special spindles up to 150,000 min−1. The spindle seating on active magnetic bearings uses attractive forces. The spindle position sensors provide the back response for the control system. The sensors send the linear output signal, and they can work in a wide range of operating temperatures. The correct bearing function is ensured by costly control electronics, which prevents faster application of these bearings in the practice. Roller “emergency” bearings are also used in the machine tool spindles carried in the active magnetic bearings (Figure 9). The main task of these bearings, which do not work at the normal spindle run, is to provide the trouble-free spindle stop in the case of the sudden electricity blackout.
\n
Figure 9.
Electrospindle with electromagnetic bearings (Ibag, HF 120 MA 80 K, nmax\n = 70,000 min−1, and P = 11 kW, Mk\n = 1.5 nm), [10].
\n
\n
\n
6.2 Roller bearings
\n
Radial angular contact ball bearings are used almost exclusively for high-frequency spindle bearings with integrated drive [11]. It is generally valid, that radial ball bearings with angular contact are recently unequivocally the most often used bearings for mounting of high-speed machine tool spindles. The reason is that their different design, their dimensional range, the contact angle values, the preload intensity, and the way of bearing arrangement in the assemblage provide the greatest scope of possibilities how to solve the compromise between the limit speed and maximum rigidity. “Spindle” bearings are manufactured in different dimensional ranges (72, 70, 719, 718) with the design of antifriction body guiding on the inside ring (B) or on the outside ring (A), with different contact angle values (12°, 15°, 25°, and 26°), with the polyamide cage (TB), with the required accuracy (P2, PA9, SP, UP), with various arrangement ways (DB, DF, DT and their combinations), with light (UL), middle (UM), or heavy preload (US) [5]. The bearings made with the higher accuracy degrees are used to seat the spindles. The axial loading capacity of the bearing increases proportionally when the contact angle increases, but the value of limit rotation frequencies decreases. It order to catch bigger radial or axial forces, the bearings are mounted in assemblages created from three, four, or five bearings. Radial load is distributed to all bearings in the group (shape arrangement), and axial load is distributed to all bearings joined behind each other (direction arrangement).
\n
\n
6.2.1 Observed parameters of the bearing groups
\n
The important parameters of the bearing groups specified to seat the working spindles at machine tools are:
run accuracy;
durability;
rigidity;
high-speed run; and
temperature.
\n\n
\n
6.2.1.1 Run accuracy
\n
The run accuracy spindle bearing system is limited by the accuracy of bearings and by the accuracy of bearing surfaces—connection parts. The accuracy of antifriction bearings is understood as the accuracy of their dimensions and run. The limit values for the accuracy of dimensions and run are mentioned in ISO 492 and ISO 199 standards. The accuracy of connection parts is understood as geometric shape and position deviations which can be admissible at the manufacture of the spindle and headstock box. The bearing manufacturer prescribes the admissible geometric shape and position deviations of bearing surfaces (Figure 10). At the assembly of bearing, it is necessary to observe matching of inside and outside bearing diameters to provide the required radial preload.
\n
Figure 10.
Prescribed shape and position deviations (SKF).
\n
\n
\n
6.2.1.2 Durability
\n
The calculation of bearing durability is generally known [6]. It is described by the international ISO 281/l standard. When durability is calculated, we usually use the modified equation of durability that expresses the durability in operation hours. The following relation is used for the bearing durability in hours:
\nCd\n is the dynamic loading capacity of the bearing [N];
\n
exponent: p = 3, for ball bearings;
\n
\np = 10/3, for needle, spherical-roller and tapered roller bearings; and
\n
\nns\n is mean frequencies of bearing rotation [min−1].
\n
The equivalent dynamic load P at roller bearings corresponds to the intensity of reactions in the particular supports. However, the methodology is not unified how to calculate the equivalent load at bearing groups made of the radial angular contact ball bearings.
\n
The spindle bearings transfer the combined radial-axial load. When the selected bearing type (selected bearings) is calculated, the combined radial-axial load is recalculated to the so-called equivalent dynamic load:
The significance of the bearing rigidity in the particular supports is considerable at the spindles having a bigger diameter, where the rigidity of the bearing assemblage in the particular supports is the limiting factor necessary to reach the required rigidity of the complete seating, as the tool how to provide its accurate operation. The total rigidity is the criterion of the body resistance against the influence of external forces.
\n
The rigidity of the bearing assemblage made from the radial angular contact ball bearings can be described mathematically as the multiple parametric function [11].
It depends on the number of bearings i, dimensional rank, size and design of bearings z, dw\n, contact angle α, preload size Fp\n, or deformations due to preload δps, and frame conditions (bearing accuracy, assembly, and cooling).
\n
Three essential states can generally take place in the bearing assemblage made from the radial ball bearings [6]:
the preload state [e.g., the assemblage joined from two shape-arranged bearings (Figure 11a)];
the preload axially loaded state [the TBT assemblage loaded by the axial force (Figure 11b)]; and
the preload radially loaded state [the QBC assemblage loaded by the radial force (Figure 11c)].
\n\n
Figure 11.
Essential states of bearing assemblages: (a) DB preload state, (b) TBT preload—axially loaded state, and (c) QBC preload -radially loaded state.
\n
Preload of the spindle bearings at the spindle assembly enables to increase the working accuracy and rigidity of the whole seating. On the other hand, the increased preload initiates the temperature origination in the bearing, which has the negative influence on critical rotation frequencies of the bearing or of the bearing assemblage. Two angular contact bearings are preload by the force Fp\n according to ČSN/STN 024615,
The axial rigidity importance comes to the foreground especially at facing, milling, drilling, and grinding. In the system “spindle-bearing,” the axial forces are almost always caught by the point-contact bearings. The axial rigidity is then given by the relation:
\n
\n\n\nC\na\n\n=\n\n\nF\na\n\n\nδ\na\n\n\n\nE6
\n
The following is valid for the approximate axial rigidity value according to [11]:
After the omission of the contact angle change due to the axial force and under the presumption that the contact angles are the same ones at both joined groups, the relation becomes the simplified form:
For the reason that the load is not distributed equally, the rigidity calculation is rather difficult and it cannot be almost realized without application of computer technology. It is necessary to determine theoretically and to verify experimentally the deformation course on the load at the preload point-contact bearing groups. The research of the bearing groups made from the radial angular contact ball bearings [12] showed that the deformation course is almost linear at the preload bearing groups up to the certain critical load. For the calculation and testing of radial ball bearings arrangement to nodes, we have developed an expert mathematical model allowing calculation of stiffness, limit frequencies, and bearing node durability.
\n
Based on this knowledge, the simplified equations for the calculation of the mean rigidity value were deduced in works [12, 13].
The following relation was deduced according to [13] for the approximate radial rigidity value of the bearing assemblage made from two shape-arranged groups:
At the omission of the contact angle change due to the axial force and under the presumption that the contact angles are the same ones at both joined groups, the relation becomes the simplified form:
Under the presumption that the contact angles \n\n\nα\n1\n\n=\n\nα\n2\n\n\nare the same ones at the shape-arranged bearings in the group ori2\n = 0 for the direction-arranged bearings in the group, the relationship between radial and axial stiffness is simplified as:
The high-speed run criterion is the quality criterion of the node regarding to the reached frequencies of rotation. Regarding to the high-speed run of the bearing nodes, the node systems are analyzed in work [6]. The particular designing solutions of the existing seating are divided into three essential groups in this work. The high-speed run parameter can reach the value K = (2–2.7).106 mm. min−1 at the special high frequency groups. For the limit values, it is suitable to use the special bearings with the optimized design, high accuracy, and with the utilization of materials having the favorable physical and mechanical properties (e.g., silicon nitride Si3N4).
where \n\n\nn\n\nl\nmax\n\n\n\n is the critical frequencies of the bearing rotation and fi\n is the coefficient describing the bearing group and conditions of its work (the number of bearings, preload, accuracy of bearings, kinematics, heat removal, lubrication, etc.). Their importance is different in dependence of the particular sources.
\n
The reduction of antifriction body dimensions results in the decrease of the centrifugal force, for which the following is valid:
where m is the antifriction body weight and ds\n is the bearing mean diameter.
\n
Such bearings are economical and reliable. The issue of decrease in centrifugal forces at high-frequency rotations is solved by reducing the weight of the rolling elements. This is achieved by changing the dimensional series of bearings and by changing the ball material.
\n
Using bearings with smaller cross-sections, for example, 718, 719 instead of bearings with bigger cross-sections (70, 72), reduces the diameter of the balls. Reducing the diameter of the rolling elements makes it possible to increase the high frequency of rotation of the bearing (Figure 12a) and at the same time increases the number of balls to achieve higher bearing stiffness (Figure 12b) [5]. With constant external diameters, the internal diameter of the bearings increases, which is suitable from the standpoint of reducing spindle deflection, increasing its drilling, and increasing the critical revolutions of the spindle.
\n
Figure 12.
Changing the dimensional series of bearings—contact ball bearings (SKF) [5] (a) relative speed capability, and (b) relative stiffness.
\n
Roller bearings as well as ball bearings can be made as so-called “hybrid ones,” which means that the bearing rings are made of steel and antifriction bodies are ceramic. The advantage of hybrid bearings by the same size compared to steel bearings is their lower centrifugal forces, frictional moment, and higher radial and axial stiffness (Figure 13). Disadvantages include the high manufacturing costs (up to 10 times) of rolling elements, still persisting problems with the homogeneity of ceramic materials, and the identification of failures.
\n
Figure 13.
Hybrid bearings (SKF).
\n
\n
\n
6.2.1.8 Temperature
\n
In the bearing groups, where no external heat sources act, the shaft temperature, the spindle temperature as well as the temperature of inside bearing rings and of the antifriction bodies are higher than the temperature of external bearing rings and of the headstock body sleeve. Due to the heat drop at the same expansibility coefficient, the dilatation of the spindle, bearing rings, and balls is bigger than the expansibility of the surrounding parts in the radial direction as well as in the axial direction. According to [11], its value is described by the equation:
For headstocks where high demands are placed on the range of rotational frequencies or temperature, it is advantageous to vary the amount of bearing preload directly during work. In order to increase the speed ranges and the service life of the spindle bearing, due consideration must be given to temperature optimization of the bearing when designing the spindle. The temperature of the bearing system varies depending on the temperature gradient, type and arrangement of the bearings (DB, DF, DT), assemblies, contact angle, bearing size, and the distances of bearings in the note and of the individual supports. There are known systems of active control of bearing preload of high-frequency headstocks and peripheral devices and sensors of important parameters, the monitoring of which has a decisive influence on ensuring correct operation of the spindle. The solution may be, for example, active piezoelectric spindle bearings preload adjustment mechanism (Figure 14a) [14]. Bearings in the rear support must also allow thermal expansion of the entire spindle. Advantageously, it is possible to minimize the change in bias in the bearing by resolving the bearing arrangement in the individual supports (Figure 14b) [5].
\n
Figure 14.
Temperature change compensation. (a) US06422757; Active piezoelectric spindle bearings preload adjustment mechanism, [14]. (b) Motor spindle SKF with movable rear support [5].
\n
\n
\n
\n
\n
\n
7. Spindle motor
\n
Desired performance and revolution characteristics place ever increasing demands on the construction of the spindle unit. The type of propulsion and bearing is the decisive component for providing the stated characteristics. Incorporating the drive directly into the spindle unit has successfully solved transmission problems at high speeds. In this way, the stress from the drive forces onto the spindle is eliminated and its accuracy is increased (Figure 15).
\n
Figure 15.
Electric spindle motors (SIEMENS).
\n
Both single-direction and alternating drives can in principle be used for integrated spindle units. Despite very good control properties, DC drives have known operational and technical drawbacks resulting from mechanical commutation devices—the commutator. For eliminating this deficiency, electronic commutation (Stromag and Bosch companies) is suitable. The use of synchronous frequency controlled drives is conditioned on the development of new hard magnetic materials [6]. In addition to the known Alnico alloys and hard ferrites, cobalt-based alloys characterized by high permanent induction (0.8–1 T) and high density are being developed, while the demagnetization curve is almost straight. An Italian company Polymotor is producing ring drives for integrated spindle units on a base of SmCO5 alloy. In an effort to reduce the consumption of rare earths and hence the cost of permanent materials, materials that do not contain rare earth are being developed. Mn-Al-C alloys are well known, as are materials containing CO, Cr, and Fe.
\n
At the present time, the majority of manufacturers of integrated drive spindle units use asynchronic frequency controlled drives due to their advantages (Table 2).
\n
Table 2.
Comparison of lubrication methods for spindle bearings [6].
\n
For securing the drive parameters, it is necessary to choose a suitable frequency shifter, which processes the frequency of the 50 Hz network with an output frequency of up to 3000 Hz. They are thyristors or transistors with sinusoidal output. The main advantage of static converters compared to rotary converters is in continuous speed change control. Acceleration and braking work in a very short time without thermal load on the engine. There is no slip during braking, which is very advantageous for precise positioning of the spindle.
\n
\n
\n
8. Peripheral
\n
\n
8.1 Clamping system
\n
High-speed machining is associated with the development of new cutting materials such as cutting ceramics, synthetic polycrystalline diamond, and cubic boron nitride. In addition to the development of cutting materials with the new physico-mechanical and chemical properties, increased attention must also be paid to the optimization of machine geometry with regard to chip removal at high machined material volumes. It will be necessary to design new holder and clamper constructions in light of the frequency of revolution, rigidity, and the flow of cooling liquids.
\n
In addition to the demands that are placed on clamping systems used in high-speed spindle units are the following constructional and technological requirements [15, 16]:
small clamp dimensions limited by spindle dimensions;
low weight, ensuring low centrifugal forces;
balancing, providing resistance to high frequencies; and
quick automatic tool or work piece exchange.
\n\n
Interfaces are used for HSC machining centers: steep taper ISO, SK, BIG PLUS (taper 7:24) and especially short taper HSK (taper 1:10), Kennametal/Widia KMTS KM4X.
\n
Clamping of the tool holder in the spindle cavity is usually done by pulling it in by means of restressed disc springs (Figure 16). The release is then a hydraulic cylinder (Figure 17). The advantage of the HSK type for high speed is that the centrifugal forces cause the collet to open, which rests on the internal cavity surface of the shank (Figure 18). Rotary turrets replace tools in less than 1 second and accuracy positioning is max. ± 3 μm.
\n
Figure 16.
Holder and clamper constructions (GMN).
\n
Figure 17.
End of spindle for clamping through the clamping shank [8].
\n
Figure 18.
Unsuitable and suitable clamping systems for high-speed spindles [DMG/Mori].
\n
Since HSC technology uses around 50,000 rpm, tools must have radial runout max. 0.003 mm and with interchangeable cutting plates (VRP) max. 0.01 mm. All tools used must be perfectly balanced.
\n
In HSC technology, the following are most commonly used as tool holders:
thermal fixture; and
hydroplastic clamp.
\n\n
The thermal clamp allows quick clamping and unclamping of tools from the fast cutting steel, including sintered carbide. Tools are exchanged with a high-frequency generator that quickly warms up the tool holder and releases it tool. The following functions are used for the correct function of the tool: monitoring the tool holder contact in the spindle cavity, checking the temperature and force of the clamping system, checking the position of the clamping cylinder and the gripper, as well as checking the suction and temperature.
\n
In the case of a hydroplastic clamp, the replacement is carried out using a hydraulic pump that squeezes the holder. Here, Pascal’s law on the spread of uniform pressure is used, which ensures even clamping of the tool in the holder.
\n
Advantages of these clamps:
rapid shrinkage and release of the holder;
the rigidity of the clamping ensures high quality of the machined surface;
good bending and radial stiffness;
clamping tools with shank h6;
circumferential runout less than 3 μm; and
use at maximum speed.
\n\n
\n
\n
8.2 Lubrication and cooling system
\n
In addition to the bearings themselves, the bearing parameters depend on the material and the quality of the surrounding parts, correct installation, and the choice of appropriate lubrication and cooling systems. These are lubrication and cooling of the contact point of the tool and work piece, lubrication and cooling of the bearings in the individual supports, and cooling of the motor and the headstock shell.
\n
The correct choice of lubricant, method of lubrication, cooling liquid, method of cooling is as important for the proper operation of the bearing as the selection of the bearing and the design of the associated components. The methods used to lubricate and cooling the spindle bearings system at machine tools are shown in Table 2. Lubrication of bearings prolongs their life; it reduces the risk of their failures due to the mechanical damage at high speed; and it leads away generated heat. The lubrication method of spindle bearings at machine tools depends on the particular operation conditions.
\n
The lubricating film thickness depends on the natural frequencies of rotation, operation temperature, and lubricant viscosity. In addition to the lubricant film thickness, it is necessary to assess the lubricant durability.
\n
Grease for lubrication consists of 90% mineral oil or petroleum oil and 10% thickener. Lime soap, soda soap, lithium soap, or barium soap is used as the thickener. Grease durability depends on its quantity, sort, the bearing type, frequencies of rotation, and temperature in the assembled state. The bearings must be run in after their lubrication, and after a certain time period, they must be again lubricated. At running in, it is also necessary to take into account that grease can be well distributed on the whole bearing, which results in equalizing of temperatures generated by mechanic losses [6].
\n
If the big accuracy is required at the spindle run, it is necessary to reduce heat. Passive friction moments that change to heat are influenced by the selected lubrication way and by the bearing design. The total passive friction moment is given:
\nf0\n is the coefficient given by the bearing design (0.7–12);
\n
\nν is the operation viscosity of oil or grease [mm2.s−1];
\n
\nn is the frequency of spindle rotation [min−1]; and
\n
\nds\n is the mean spindle diameter [mm].
\n
Lubrication by oil is used mainly in those cases where operation frequencies of rotation also require removal of generated heat from the bearing. At lubrication of the precise spindle bearings, it is necessary to use a small oil quantity to reach the high-quality bearing lubrication. The most widely used lubricating methods are:
oil mist lubrication—the oil mist is produced in an atomizer and conveyed to the bearings by an air current. The air current also serves to cool the bearings and the slightly higher pressure prevents contamination from penetration;
oil-air lubrication—the oil is conveyed to the bearing in droplets by compressed air. The droplet size and the intervals between two droplets are controlled; and
Oil-jet lubrication (cooling lubrication)—considerable amounts of oil are carried through the bearing by injection, the frictional heat generated in the bearing is dissipated. The cooling of the oil is achieved, for example, with an oil-to-air heat exchanger.
\n\n
\nTable 2 describes various lubrication technologies and Table 3 gives an overview of the individual components and peripheral devices used by selected manufacturers of electric spindles (Table 3).
\n
\n
\n
\n
\n
\n
\n
\n
\n\n
\n
Producer
\n
Performance range [kW]
\n
Revolutions range [min−1]
\n
Lubrication
\n
Cooling
\n
Drive
\n
Technological operations
\n
\n\n\n
\n
ENIMS
\n
6.5
\n
48–5200
\n
Oil mist
\n
Air liquid
\n
AC
\n
Tu
\n
\n
\n
OMLAT
\n
4.5–48.5
\n
5000–40,000
\n
Oil mist grease
\n
Air
\n
AC
\n
Mi, Dr., Gr
\n
\n
\n
IBAG
\n
3–42
\n
3000–80,000
\n
Oil-air grease
\n
Air liquid
\n
AC
\n
Mi, Dr
\n
\n
\n
GMN
\n
3–40
\n
9000–60,000
\n
Oil mist Oil-jet grease
\n
Liquid
\n
AC
\n
Mi, Dr., Gr
\n
\n
\n
FAG
\n
2.5–20
\n
20,000–45,000
\n
Oil-jet minim. amount
\n
Liquid
\n
AC
\n
Gr, Dr., Mi
\n
\n
\n
SZM
\n
10–15
\n
20,000–75,000
\n
Oil-jet grease
\n
Air
\n
AC
\n
Mi, Gr
\n
\n
\n
ITW
\n
15
\n
22,000–36,000
\n
Oil mist
\n
Air
\n
AC
\n
Mi, Gr
\n
\n
\n
SKF
\n
5.5–16
\n
10,000–30,000
\n
Oil mist Oil-air
\n
Liquid
\n
AC
\n
Gr, Mi
\n
\n
\n
MODIGS
\n
1.4
\n
70–2160
\n
Grease
\n
Liquid
\n
DC
\n
Gr, Mi
\n
\n
\n
FORTUNA
\n
0.45–15
\n
12,000–18,000
\n
Oil mist
\n
Liquid
\n
AC
\n
Gr, Dr., Mi
\n
\n
\n
SETKO
\n
3.7
\n
400–10,000
\n
Grease
\n
Liquid
\n
\n
Fr, Dr
\n
\n
\n
PRECESI
\n
0.17–6
\n
7500–12,000
\n
Oil mist
\n
Liquid
\n
AC
\n
Fr, Dr., Gr
\n
\n\n
Table 3.
Components and peripheral devices used by selected manufacturers of electric spindles.
Machine units with AC integrated drive, DC, direct drive; Tu, turning; Mi, milling; Dr, drilling; Gr, grinding.
\n
\n
\n
\n
9. Realized outputs
\n
The spindle unit is determined by the structural parameters of the machine tool.
\n
In accordance with the growing requirements for production and precision of machine tools, the requirements for the design and technical execution of machine tool headstocks are increasing. The headstock of a machine tool is now a mechatronic, highly sophisticated system in which internal systems with external peripherals must interact. The design, research and development of new types of headstocks is not possible today without high-quality computing and simulation software, high-performance computing, testing equipment, and the necessary experience. For our headstock design, we have developed:
special software that enables the calculation of the load, stiffness, and durability of rolling bearings used for the bearing of machine tool spindles [11, 12, 13]. Our methodology of calculation of bearing nodes associated from radial ball bearings angular contact is original. At the same time, the software enables to calculate the optimal distance of bearing supports with respect to overall maximum stiffness, running accuracy, and thermal expansion according to the arrangement of bearings in individual nodes as well as thermal expansion of the whole spindle bearing system; and
special testing equipment for measuring the accuracy of running, temperature, and stiffness of bearing nodes made of radial ball bearings with angular contact. The experimental bench (Figure 19) enables the determination of required parameters of nodes arrangement by up to 5 bearings [6, 11]. Testing is carried out under different operating conditions.
\n\n
Figure 19.
Laboratory for measuring: (a) testing equipment for measuring bearing nodes; and (b) test bench for testing functional models.
\n
The results of our work are designed more headstocks of machine tools. At our institute, we developed headstocks for CNC machine tools for the companies TOS Lipník and TOS Kuřim. The headstocks developed for SBL CNC lathes manufactured by the company Trens Trenčín deserve special attention [17]. The headstocks of the 300, 500, and 700 series developed at our workplace and the first lathes SBL was first time at the exhibition in Nitra 2000 and at the exhibition in Düseldorf 2004 presented. The SBL series lathes with the listed headstocks are still produced and are successful in the market.
\n
Well known is our design of high-speed headstock with two drives. The advantage of the original solution is the possibility of using a high torque moment at low revs, as well as the principle of achieving high resultant revolutions of a double-mounted spindle driven by two drives [11]. The headstock is applied to a wood lathe in the company Šustrik.
\n
An example of a new functional model of an electric headstock for a grinding machine is shown Figure 20 [18]. It is a design of a headstock designed on the basis of modular components of an AC motor (stator, rotor, and metering system) and compact control system of the IMB Indramat drive. The functional model is preferably used in our laboratories for ultrasonic grinding.
\n
Figure 20.
Motor spindles for grinding machine tool [18].
\n
When designing all headstocks, we use the V-2.16 headstock application software. The technical parameters of the rolling bearing nodes, such as axial and radial stiffness, maximum speed, temperature, and running accuracy, are tested in our laboratories. Both the software and the experimental stand were developed at our workplace.
\n
\n
\n
10. Conclusion
\n
The technical level of fully automated flexible production systems has reached a degree at which accompanying working times and instruments are reduced to a minimum. Further increases in output are therefore possible by reducing the main production times.
\n
This is possible by increasing cutting speeds—high-speed machining. Research in the field of high-speed cutting shows that, along with the reduction of lead times, cutting accuracy, productivity and machined surface quality are significantly improved.
\n
In the chapter, requirements, characteristics, and development tendencies of the whole concept of construction of a machine, as well as construction nodes and elements of machine for high-speed cutting are described. With respect to the individual technological operations and the range and diversity of the required parameters, it is clean that at this time, it is not possible to design and universal machining unit—headstock. This requires a modular construction of the machining tool and individual peripheries that make possible a rapid change of the machining unit with the required revolution and performance characteristics.
\n
The headstock is a determining structural node affected technological parameters machine tool. For high-speed machining, headstocks with built-in drive are used “Electrospindles.”
\n
The results of the analysis showed that electromagnetic and rolling spindles are used to accommodate the spindles of high-speed headstocks. Exceptionally with lower rigidity requirements, an aero-static bearing can also be used. The most widely rolling bearings used machine tool spindle support are nodes—formed from radial ball bearings with angular contact. They are reliable enough, cost-effective and, given the wide range of combinations, they can optimally meet the contradictory requirements of stiffness and maximum speed. Hybrid ball bearings are used for the highest rotational speeds but are very expensive.
\n
In terms of drives, both single-direction and alternating drives can be used in the principle for integrated spindle units. Despite very good control properties, DC drives have known operational and technical drawbacks resulting from commutation devices. They are used less than AC drives. From the point of view of lubrication, the oil-air system is used for the highest rotational frequencies, while grease lubrication is still used for the lowest rotational requirements.
\n
The headstock is a complicated mechatronic node with a system of internal elements and external peripherals. Designers must, in addition to complicated computer systems, perfectly master the demands placed on the headstock and the interoperability of individual elements and peripherals. New non-traditional materials (SI3N4, SmCO5 alloy) as well as progressive design technologies and design solutions are used to achieve the best technical parameters of these headstocks. At the end of the chapter, we present our results and experience in the design of headstocks of machine tools.
\n
\n
Acknowledgments
\n
The research presented in this paper is an outcome of the project No. APVV-16-0476 “Research and development of the progressive design of the high speed rotor mounting in spinning machine” funded by the Slovak Research and Development Agency.
\n
\n',keywords:"headstock, high-speed cutting, ball bearings with angular contact, design, testing",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/72436.pdf",chapterXML:"https://mts.intechopen.com/source/xml/72436.xml",downloadPdfUrl:"/chapter/pdf-download/72436",previewPdfUrl:"/chapter/pdf-preview/72436",totalDownloads:493,totalViews:0,totalCrossrefCites:0,dateSubmitted:"October 13th 2019",dateReviewed:"May 4th 2020",datePrePublished:"June 9th 2020",datePublished:"October 21st 2020",dateFinished:"June 9th 2020",readingETA:"0",abstract:"The progressive technological growth in developed industrial countries is characterized by the increasing range of manufactured parts, the variety of their shapes, and the development and usage of new non-traditional materials. At the same time, demands for high quality and production efficiency must be fulfilled. The essential function of machine tools is to make workpiece surfaces with the required geometry and with the required surface quality under economically efficient conditions. A significant benefit in increasing the efficiency and quality of machined surfaces was the development of high-speed machining. With the application of this machining method, the overall concept of the machine tool and the construction of its individual nodes have changed. The headstock has a significant impact on the quality of the final product and the overall productivity of the machine tool. Machine tools with integrated drive headstocks offer the users much greater performance and reliability. The aim of the presented chapter is the analysis of high-speed machining technology, a description of the structures of high-frequency headstocks and their individual parts, along with the design of a headstock with an integrated drive for the specific case of a machine tool.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/72436",risUrl:"/chapter/ris/72436",signatures:"Ľubomír Šooš",book:{id:"9266",type:"book",title:"Machine Tools",subtitle:"Design, Research, Application",fullTitle:"Machine Tools - Design, Research, Application",slug:"machine-tools-design-research-application",publishedDate:"October 21st 2020",bookSignature:"Ľubomír Šooš and Jiri Marek",coverURL:"https://cdn.intechopen.com/books/images_new/9266.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83962-351-6",printIsbn:"978-1-83962-350-9",pdfIsbn:"978-1-83962-352-3",isAvailableForWebshopOrdering:!0,editors:[{id:"141212",title:"Prof.",name:"Ľubomír",middleName:null,surname:"Šooš",slug:"lubomir-soos",fullName:"Ľubomír Šooš"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"141212",title:"Prof.",name:"Ľubomír",middleName:null,surname:"Šooš",fullName:"Ľubomír Šooš",slug:"lubomir-soos",email:"lubomir.soos@stuba.sk",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/141212/images/system/141212.jpg",institution:{name:"Slovak University of Technology in Bratislava",institutionURL:null,country:{name:"Slovakia"}}}],sections:[{id:"sec_1",title:"1. History, development, and advantages of speed machining",level:"1"},{id:"sec_2",title:"2. Parameters of high-speed machining",level:"1"},{id:"sec_3",title:"3. Headstock—heart of machine tool",level:"1"},{id:"sec_4",title:"4. Box of headstock",level:"1"},{id:"sec_5",title:"5. Work spindle",level:"1"},{id:"sec_6",title:"6. Spindle bearing system",level:"1"},{id:"sec_6_2",title:"6.1 Electromagnetic bearings",level:"2"},{id:"sec_7_2",title:"6.2 Roller bearings",level:"2"},{id:"sec_7_3",title:"6.2.1 Observed parameters of the bearing groups",level:"3"},{id:"sec_7_4",title:"6.2.1.1 Run accuracy",level:"4"},{id:"sec_8_4",title:"6.2.1.2 Durability",level:"4"},{id:"sec_9_4",title:"6.2.1.3 Rigidity",level:"4"},{id:"sec_10_4",title:"6.2.1.4 Axial rigidity",level:"4"},{id:"sec_11_4",title:"6.2.1.5 Radial rigidity",level:"4"},{id:"sec_12_4",title:"6.2.1.6 Directional rigidity",level:"4"},{id:"sec_13_4",title:"6.2.1.7 High-speed run",level:"4"},{id:"sec_14_4",title:"6.2.1.8 Temperature",level:"4"},{id:"sec_18",title:"7. Spindle motor",level:"1"},{id:"sec_19",title:"8. Peripheral",level:"1"},{id:"sec_19_2",title:"8.1 Clamping system",level:"2"},{id:"sec_20_2",title:"8.2 Lubrication and cooling system",level:"2"},{id:"sec_22",title:"9. Realized outputs",level:"1"},{id:"sec_23",title:"10. Conclusion",level:"1"},{id:"sec_24",title:"Acknowledgments",level:"1"}],chapterReferences:[{id:"B1",body:'\nSchmockel D, Arnold W, Scherer J. Hochgeschwindigketsfräsen von Aluminium legierungen. VDI Zeitschrift. 1980;122(19):243-245\n'},{id:"B2",body:'\nSchulz H, Scherer J. Aktueller stnd des verbundforschurgsprojekts, Hochgeschwindigkeitsfräsen. Die Maschine. 1987;10:14-18\n'},{id:"B3",body:'\nPasko R, Przybylski L, Slodski B. High speed machining (HSM)—The effective way of modern cutting. In: International Workshop CA Systems and Technologies. pp. 72-79. [Accessed: 24 April 2003]\n'},{id:"B4",body:'\nKönig W. Technologische Aspekte der Hochgeschwindigkeitzerspannung. Vorträg ansläβlich einer HGF—Tagung 17–18.4.1980. Eigenverlag der TH Aachen; 1980\n'},{id:"B5",body:'\nAvailable from: https://www.google.com/search?q=Skf+Motor+spindles\n\n'},{id:"B6",body:'\nMarek J et al. Designing of CNC Machine Tools. Praha: MM Publishing, s. r. o; 2010. p. 419 s. ISBN: 978-80_254–7980-3\n'},{id:"B7",body:'\nLee D, Sin H, Sun N. Manufacturing of a graphite epoxy composite spindle for a machine tool. Annals CIRP. 1985;34:365-369\n'},{id:"B8",body:'\nDemeč P. Accuracy of Machine Tools and Its Mathematic Modelling. 1st ed. Košice, Vienala: Technical University in Košice; 2001. p. 146. ISBN: 80-7099-620-X (in Slovak)\n'},{id:"B9",body:'\nAvailable from: https://www.magnetic.waukbearing.com\n\n'},{id:"B10",body:'\nAvailable from: http://www.ibag.ch/en/downloads.html\n\n'},{id:"B11",body:'\nŠooš Ľ. Chapter: Radial ball bearings with angular contact in machine tools. In: Sehgal R, editor. Performance Evaluation of Bearings. Novi Sad, Croatia: Intech Prepress; 2012. pp. 49-92, 240. ISBN: 978-953-51-0786-6\n'},{id:"B12",body:'\nŠooš Ľ. New methodology calculations of radial stiffness nodal points spindle machine tool. In: International symposium on Advanced Engineering & Applied Management—40th Anniversary in Higher Education: Romania/Hunedoara/4–5 November 2010. Hunedoara: Faculty of Engineering Hunedoara; 2010. pp. III-99-III-104. ISBN: 978-973-0-09340-7\n'},{id:"B13",body:'\nŠooš Ľ. Approximate methodology calculations of stiffness nodal points. World Academy of Science, Engineering and Technology. 2011;7(80):1390-1395\n'},{id:"B14",body:'\nUS Patent: US 6,422,757 B1 Active piezoelectric spindle bearing preload adjustment mechanism. July 23 2002\n'},{id:"B15",body:'\nMarek J et al. Designing of CNC Machine Tools. Praha: MM Publishing, s. r. o.; 2015. p. 727 s. ISBN: 978-80-260-8637-6\n'},{id:"B16",body:'\nAvailable from: http://www.gmn/en/downloads.html\n\n'},{id:"B17",body:'\nŠooš Ľ. Spindle–Housing system SBL 500 CNC. Eksploatacja i Niezawodnošč = Maintenance and reliability. 2008;2:53-56\n'},{id:"B18",body:'\nGreguš Kolár J. High speed motor spindles for grinding (in Slovak). Bratislava: FME STU; 2015. p. 67\n'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Ľubomír Šooš",address:"lubomir.soos@stuba.sk",affiliation:'
Institute of Production Systems, Environmental Technology and Quality Management of the Faculty of Mechanical Engineering of STU in Bratislava, Bratislava, Slovakia
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Hunter",authors:[{id:"176855",title:"Dr.",name:"Wayne",middleName:null,surname:"Hunter",slug:"wayne-hunter",fullName:"Wayne Hunter"},{id:"177693",title:"Dr.",name:"Eduardo",middleName:null,surname:"Andrade",slug:"eduardo-andrade",fullName:"Eduardo Andrade"}]},{id:"43162",doi:"10.5772/52704",title:"Non-Viral Delivery Systems in Gene Therapy",slug:"non-viral-delivery-systems-in-gene-therapy",totalDownloads:4214,totalCrossrefCites:12,totalDimensionsCites:32,abstract:null,book:{id:"3509",slug:"gene-therapy-tools-and-potential-applications",title:"Gene Therapy",fullTitle:"Gene Therapy - Tools and Potential Applications"},signatures:"Alicia Rodríguez Gascón, Ana del Pozo-Rodríguez and María Ángeles Solinís",authors:[{id:"156696",title:"Dr.",name:"Alicia",middleName:null,surname:"Rodríguez Gascón",slug:"alicia-rodriguez-gascon",fullName:"Alicia Rodríguez Gascón"}]},{id:"30029",doi:"10.5772/34438",title:"The Legume Root Nodule: From Symbiotic Nitrogen Fixation to Senescence",slug:"the-legume-root-nodule-from-symbiotic-nitrogen-fixation-to-senescence",totalDownloads:4698,totalCrossrefCites:18,totalDimensionsCites:32,abstract:null,book:{id:"1446",slug:"senescence",title:"Senescence",fullTitle:"Senescence"},signatures:"Laurence Dupont, Geneviève Alloing, Olivier Pierre, Sarra El Msehli, Julie Hopkins, Didier Hérouart and Pierre Frendo",authors:[{id:"100143",title:"Dr.",name:"Pierre",middleName:null,surname:"Frendo",slug:"pierre-frendo",fullName:"Pierre Frendo"},{id:"100842",title:"Dr.",name:"Laurence",middleName:null,surname:"Dupont",slug:"laurence-dupont",fullName:"Laurence Dupont"},{id:"100848",title:"Dr.",name:"Geneviève",middleName:null,surname:"Alloing",slug:"genevieve-alloing",fullName:"Geneviève Alloing"},{id:"100852",title:"MSc.",name:"Sarra",middleName:null,surname:"El Msehli",slug:"sarra-el-msehli",fullName:"Sarra El Msehli"},{id:"100854",title:"MSc.",name:"Olivier",middleName:null,surname:"Pierre",slug:"olivier-pierre",fullName:"Olivier Pierre"},{id:"100859",title:"BSc.",name:"Julie",middleName:null,surname:"Hopkins",slug:"julie-hopkins",fullName:"Julie Hopkins"},{id:"100860",title:"Prof.",name:"Didier",middleName:null,surname:"Hérouart",slug:"didier-herouart",fullName:"Didier Hérouart"}]},{id:"49590",doi:"10.5772/61807",title:"Management of Insect Pest by RNAi — A New Tool for Crop Protection",slug:"management-of-insect-pest-by-rnai-a-new-tool-for-crop-protection",totalDownloads:3719,totalCrossrefCites:17,totalDimensionsCites:28,abstract:"The fast-growing human population requires the development of new agricultural technologies to meet consumers´ demand, while minimizing environmental impacts. Insect pests are one of the main causes for losses in agriculture production, and current control technologies based on pesticide application or the use of transgenic crops expressing Bacillus thuringiensis toxin proteins are facing efficacy challenges. Novel approaches to control pests are urgently necessary. RNA interference (RNAi) is a gene silencing mechanism triggered by providing double-stranded RNA (dsRNA), that when ingested into insects can lead to death or affect the viability of the target pest. Transgenic plants expressing dsRNA version of insect specific target genes are the new generation of resistant plants. However, the RNAi mechanism is not conserved among insect orders, and its elucidation is the key to develop commercial RNAi crops. In this chapter, we review the core RNAi pathway in insects and the dsRNA uptake, amplification, and spread of systemic silencing signals in some key insect species. We also highlight some of the experimental steps before developing an insect-pest-resistant “RNAi plant”. Lastly, we review some of the most recent development studies to control agricultural insect pests by RNAi transgenic plants.",book:{id:"5090",slug:"rna-interference",title:"RNA Interference",fullTitle:"RNA Interference"},signatures:"Thais Barros Rodrigues and Antonio Figueira",authors:[{id:"176770",title:"Dr.",name:"Thais B.",middleName:null,surname:"Rodrigues",slug:"thais-b.-rodrigues",fullName:"Thais B. Rodrigues"},{id:"176820",title:"Dr.",name:"Antonio",middleName:null,surname:"Figueira",slug:"antonio-figueira",fullName:"Antonio Figueira"}]}],mostDownloadedChaptersLast30Days:[{id:"50471",title:"Molecular Mechanisms of Skin Aging and Rejuvenation",slug:"molecular-mechanisms-of-skin-aging-and-rejuvenation",totalDownloads:5110,totalCrossrefCites:6,totalDimensionsCites:13,abstract:"The aging process in the skin is complex and influenced by more intrinsic and extrinsic factors than any other body organ. The effects of these two types of factors overlap for the most part. The combined effects of these two aging processes also affect dermal matrix alterations. The main clinical signs of skin aging include wrinkling and irregular pigmentation, which are influenced by a combination of intrinsic and extrinsic (e.g., UV radiation, heat, smoking, and pollutants) factors. Histologically, collagen decreases, and the dermis is replaced by abnormal elastic fibers as a cause of wrinkle formation through the loss of skin elasticity. There have been numerous studies of skin aging performed to elucidate the underlying molecular mechanisms and to develop various antiaging therapeutics and preventive strategies. We summarized the molecular mechanisms and treatments of skin aging. Mainly UV radiation induces ROS formation and DNA damage, leading to increased production of MMPs and decreased production of collagen in keratinocytes and fibroblasts, which reflect the central aspects of skin aging. Besides UV radiation exposure, extrinsic factors including tobacco smoking, exposure to environmental pollutants, infrared radiation, and heat contribute to premature skin aging. Like UV radiation, these factors cause ROS formation and increase expression of MMPs, thus accelerating skin aging by inducing extracellular matrix (ECM) degradation. Accumulated collagen fibrils inhibit the new collagen synthesis and account for the further degradation of the ECM through this positive feedback loop. Accumulating evidence for molecular mechanisms of skin aging should provide clinicians with an expanding spectrum of therapeutic targets in the treatment of skin aging.",book:{id:"5258",slug:"molecular-mechanisms-of-the-aging-process-and-rejuvenation",title:"Molecular Mechanisms of the Aging Process and Rejuvenation",fullTitle:"Molecular Mechanisms of the Aging Process and Rejuvenation"},signatures:"Miri Kim and Hyun Jeong Park",authors:[{id:"47695",title:"Prof.",name:"Hyun Jeong",middleName:null,surname:"Park",slug:"hyun-jeong-park",fullName:"Hyun Jeong Park"},{id:"185767",title:"Prof.",name:"Miri",middleName:null,surname:"Kim",slug:"miri-kim",fullName:"Miri Kim"}]},{id:"49637",title:"RNA Interference Technology — Applications and Limitations",slug:"rna-interference-technology-applications-and-limitations",totalDownloads:4073,totalCrossrefCites:1,totalDimensionsCites:1,abstract:"RNA interference (RNAi), an evolutionarily conserved mechanism triggered by double-stranded RNA (dsRNA), causes gene silencing in a sequence-specific manner. RNAi evolved naturally to mediate protection from both endogenous and exogenous pathogenic nucleic acids and to modulate gene expression. Multiple technological advancements and precision in gene targeting have allowed a plethora of potential applications, ranging from targeting infections in crop plants to improving health in human patients, which have been reviewed in this chapter.",book:{id:"5090",slug:"rna-interference",title:"RNA Interference",fullTitle:"RNA Interference"},signatures:"Devi Singh, Sarika Chaudhary, Rajendra Kumar, Preeti Sirohi,\nKamiya Mehla, Anil Sirohi, Shashi Kumar, Pooran Chand and Pankaj\nKumar Singh",authors:[{id:"176625",title:"Prof.",name:"Devi",middleName:null,surname:"Singh",slug:"devi-singh",fullName:"Devi Singh"},{id:"176744",title:"Ms.",name:"Preeti",middleName:null,surname:"Sirohi",slug:"preeti-sirohi",fullName:"Preeti Sirohi"},{id:"176745",title:"Dr.",name:"Rajendra",middleName:null,surname:"Kumar",slug:"rajendra-kumar",fullName:"Rajendra Kumar"},{id:"176746",title:"Mrs.",name:"Sarika",middleName:null,surname:"Chaudhary",slug:"sarika-chaudhary",fullName:"Sarika Chaudhary"},{id:"176747",title:"Dr.",name:"Kamiya",middleName:null,surname:"Mehla",slug:"kamiya-mehla",fullName:"Kamiya Mehla"},{id:"176748",title:"Dr.",name:"Pankaj Kumar",middleName:null,surname:"Singh",slug:"pankaj-kumar-singh",fullName:"Pankaj Kumar Singh"},{id:"176749",title:"Dr.",name:"Shashi",middleName:null,surname:"Kumar",slug:"shashi-kumar",fullName:"Shashi Kumar"},{id:"176809",title:"Dr.",name:"Pooran",middleName:null,surname:"Chand",slug:"pooran-chand",fullName:"Pooran Chand"}]},{id:"43280",title:"Gene Therapy for Diabetic Retinopathy – Targeting the Renin-Angiotensin System",slug:"gene-therapy-for-diabetic-retinopathy-targeting-the-renin-angiotensin-system",totalDownloads:2439,totalCrossrefCites:2,totalDimensionsCites:2,abstract:null,book:{id:"3509",slug:"gene-therapy-tools-and-potential-applications",title:"Gene Therapy",fullTitle:"Gene Therapy - Tools and Potential Applications"},signatures:"Qiuhong Li, Amrisha Verma, Ping Zhu, Bo Lei, Yiguo Qiu, Takahiko Nakagawa, Mohan K Raizada and William W Hauswirth",authors:[{id:"155578",title:"Dr.",name:"Qiuhong",middleName:null,surname:"Li",slug:"qiuhong-li",fullName:"Qiuhong Li"}]},{id:"49416",title:"Microinjection-Based RNA Interference Method in the Water Flea, Daphnia pulex and Daphnia magna",slug:"microinjection-based-rna-interference-method-in-the-water-flea-daphnia-pulex-and-daphnia-magna",totalDownloads:2176,totalCrossrefCites:4,totalDimensionsCites:7,abstract:"It is well known that most daphnid species have several attractive life history characteristics such as cyclical parthenogenesis, environmental sex determination, and predator-induced defense formation. Recent advances in high-throughput omics technologies make it easy to obtain a huge number of potential candidate factors involved in environmental stimuli-triggered phenotypic alterations. Furthermore, our group has developed a microinjection system to introduce foreign materials such as nucleotides and chemicals into the early-stage (one-cell stage) egg of Daphnia pulex and Daphnia magna. Consequently, we established a microinjection-based RNAi system that allows arbitrary gene functions to be investigated. However, this microinjection system does not seem to have pervaded in the daphnid research community due to its low throughput and high level of skills required. In this chapter, we review the microinjection method and its RNAi system in water fleas, D. pulex and D. magna, providing some technical tips and making challenging proposals for the development of novel high-throughput RNAi methods. Finally, we provide an overview of recently developed gene functional analysis methods such as overexpression and genome-editing systems.",book:{id:"5090",slug:"rna-interference",title:"RNA Interference",fullTitle:"RNA Interference"},signatures:"Kenji Toyota, Shinichi Miyagawa, Yukiko Ogino and Taisen Iguchi",authors:[{id:"92826",title:"Dr.",name:"Taisen",middleName:null,surname:"Iguchi",slug:"taisen-iguchi",fullName:"Taisen Iguchi"},{id:"176835",title:"Dr.",name:"Kenji",middleName:null,surname:"Toyota",slug:"kenji-toyota",fullName:"Kenji Toyota"}]},{id:"55603",title:"RNA‐seq: Applications and Best Practices",slug:"rna-seq-applications-and-best-practices",totalDownloads:3706,totalCrossrefCites:7,totalDimensionsCites:8,abstract:"RNA‐sequencing (RNA‐seq) is the state‐of‐the‐art technique for transcriptome analysis that takes advantage of high‐throughput next‐generation sequencing. Although being a powerful approach, RNA‐seq imposes major challenges throughout its steps with numerous caveats. There are currently many experimental options available, and a complete comprehension of each step is critical to make right decisions and avoid getting into inconclusive results. A complete workflow consists of: (1) experimental design; (2) sample and library preparation; (3) sequencing; and (4) data analysis. RNA‐seq enables a wide range of applications such as the discovery of novel genes, gene/transcript quantification, and differential expression and functional analysis. This chapter will encompass the main aspects from sample preparation to downstream data analysis. It will be discussed how to obtain high‐quality samples, replicates amount, library preparation, sequencing platforms and coverage, focusing on best recommended practices based on specialized literature. Basic techniques and well‐known algorithms are presented and discussed, guiding both beginners and experienced users in the implementation of reliable experiments.",book:{id:"5944",slug:"applications-of-rna-seq-and-omics-strategies-from-microorganisms-to-human-health",title:"Applications of RNA-Seq and Omics Strategies",fullTitle:"Applications of RNA-Seq and Omics Strategies - From Microorganisms to Human Health"},signatures:"Michele Araújo Pereira, Eddie Luidy Imada and Rafael Lucas Muniz\nGuedes",authors:[{id:"202103",title:"Ph.D. Student",name:"Michele",middleName:"Araújo",surname:"Pereira",slug:"michele-pereira",fullName:"Michele Pereira"},{id:"202456",title:"MSc.",name:"Eddie Luidy",middleName:null,surname:"Imada",slug:"eddie-luidy-imada",fullName:"Eddie Luidy Imada"},{id:"202460",title:"Dr.",name:"Rafael",middleName:null,surname:"Guedes",slug:"rafael-guedes",fullName:"Rafael Guedes"}]}],onlineFirstChaptersFilter:{topicId:"419",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:87,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:98,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:27,numberOfPublishedChapters:287,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:9,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:139,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:0,numberOfUpcomingTopics:2,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!1},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:107,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:10,numberOfPublishedChapters:103,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:2,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:0,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!1},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:10,numberOfOpenTopics:4,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. 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His research interests and specialties include financial econometrics, financial economics, international economics and finance, housing markets, financial markets, among others.",institutionString:null,institution:{name:"University of Southampton",institutionURL:null,country:{name:"United Kingdom"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:3,paginationItems:[{id:"86",title:"Business and Management",coverUrl:"https://cdn.intechopen.com/series_topics/covers/86.jpg",isOpenForSubmission:!0,editor:{id:"128342",title:"Prof.",name:"Vito",middleName:null,surname:"Bobek",slug:"vito-bobek",fullName:"Vito Bobek",profilePictureURL:"https://mts.intechopen.com/storage/users/128342/images/system/128342.jpg",biography:"Dr. Vito Bobek works as an international management professor at the University of Applied Sciences FH Joanneum, Graz, Austria. He has published more than 400 works in his academic career and visited twenty-two universities worldwide as a visiting professor. Dr. Bobek is a member of the editorial boards of six international journals and a member of the Strategic Council of the Minister of Foreign Affairs of the Republic of Slovenia. He has a long history in academia, consulting, and entrepreneurship. His own consulting firm, Palemid, has managed twenty significant projects, such as Cooperation Program Interreg V-A (Slovenia-Austria) and Capacity Building for the Serbian Chamber of Enforcement Agents. He has also participated in many international projects in Italy, Germany, Great Britain, the United States, Spain, Turkey, France, Romania, Croatia, Montenegro, Malaysia, and China. Dr. Bobek is also a co-founder of the Academy of Regional Management in Slovenia.",institutionString:"Universities of Applied Sciences FH Joanneum, Austria",institution:null},editorTwo:{id:"293992",title:"Dr.",name:"Tatjana",middleName:null,surname:"Horvat",slug:"tatjana-horvat",fullName:"Tatjana Horvat",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hXb0hQAC/Profile_Picture_1642419002203",biography:"Tatjana Horvat works as a professor for accountant and auditing at the University of Primorska, Slovenia. She is a Certified State Internal Auditor (licensed by Ministry of Finance RS) and Certified Internal Auditor for Business Sector and Certified accountant (licensed by Slovenian Institute of Auditors). At the Ministry of Justice of Slovenia, she is a member of examination boards for court expert candidates and judicial appraisers in the following areas: economy/finance, valuation of companies, banking, and forensic investigation of economic operations/accounting. At the leading business newspaper Finance in Slovenia (Swedish ownership), she is the editor and head of the area for business, finance, tax-related articles, and educational programs.",institutionString:null,institution:{name:"University of Primorska",institutionURL:null,country:{name:"Slovenia"}}},editorThree:null},{id:"87",title:"Economics",coverUrl:"https://cdn.intechopen.com/series_topics/covers/87.jpg",isOpenForSubmission:!0,editor:{id:"327730",title:"Prof.",name:"Jaime",middleName:null,surname:"Ortiz",slug:"jaime-ortiz",fullName:"Jaime Ortiz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002zaOKZQA2/Profile_Picture_1642145584421",biography:"Dr. Jaime Ortiz holds degrees from Chile, the Netherlands, and the United States. He has held tenured faculty, distinguished professorship, and executive leadership appointments in several universities around the world. 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